# US 7,407,785 B2 · Human DNase I hyperactive variants

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- Number: US 7,407,785 B2
- Document ID: US7407785B2
- Status: Granted
- Kind: B2
- Application number: 10/838,691
- Filed: 2004-05-03
- Published: 2005-08-04
- Granted: 2008-08-05
- Earliest claimed: 1996-06-14
- Assignees: Genentech, Inc.
- Inventors: Robert A. Lazarus; Clark Qun Pan
- Web page: https://patentgrep.com/patent/US7407785B2

## CPC

- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/12: Mucolytics
- A61P 37/00: Drugs for immunological or allergic disorders
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

The present invention relates to amino acid sequence variants of human DNase I that have increased DNA-hydrolytic activity. The invention provides nucleic acid sequences encoding such hyperactive variants, thereby enabling the production of these variants in quantities sufficient for clinical use. The invention also relates to pharmaceutical compositions and therapeutic uses of hyperactive-variants of human DNase I.

## Claims

### Claim 1

A variant of human DNase I comprising an amino acid sequence having at least 90% sequence identity with the amino acid sequence of SEQ ID NO: 1, wherein the amino acid residue corresponding to position 205 of the polypeptide of SEQ ID NO: 1 is a lysine residue, and wherein said variant has DNA-hydrolytic activity.

### Claim 2 (depends on 1)

A pharmaceutical composition comprising the human DNase I variant of claim 1 and a pharmaceutically acceptable excipient.

### Claim 3

A variant of human DNase I comprising the amino acid sequence of SEQ ID NO: 1 except for a single amino acid substitution at position 205 of SEQ ID NO: 1.

### Claim 4 (depends on 1)

The variant of human DNase I according to claim 1 comprising an amino acid sequence having at least 98% sequence identity with the amino acid sequence of SEQ ID NO: 1.

### Claim 5 (depends on 1)

The variant of human DNase I according to claim 1 comprising an amino acid sequence having at least 95% sequence identity with the amino acid sequence of SEQ ID NO: 1.